Characterization of a Rare Single α-Globin Gene Deletion in a Chinese Woman with Hb H Disease

Abstract We report the characterization of the amount of beta mRNA in a Kurdish Jewish population with beta0-thalassemia using the same methods employed for characterization of the Catania and Ferrara beta0 patients. We found very low amounts of beta mRNA sequences, consistent with the presence of beta0-thalassemia of the beta mRNA-negative population type. In addition, no globin gene deletion was detected that could account for the absence of beta mRNA.

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Absence of beta mRNA in beta0-thalassemia in Kurdish Jews

Blood ◽

10.1182/blood.v52.4.735.bloodjournal524735 ◽

1978 ◽

Vol 52 (4) ◽

pp. 735-739

Author(s):

F Ramirez ◽

D Starkman ◽

A Bank ◽

H Kerem ◽

G Cividalli ◽

...

Keyword(s):

Jewish Population ◽

Gene Deletion ◽

Globin Gene ◽

Population Type ◽

Negative Population

We report the characterization of the amount of beta mRNA in a Kurdish Jewish population with beta0-thalassemia using the same methods employed for characterization of the Catania and Ferrara beta0 patients. We found very low amounts of beta mRNA sequences, consistent with the presence of beta0-thalassemia of the beta mRNA-negative population type. In addition, no globin gene deletion was detected that could account for the absence of beta mRNA.

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Molecular characterization of a beta zero-thalassemia resulting from a 1.4 kilobase deletion

Blood ◽

10.1182/blood.v72.2.636.636 ◽

1988 ◽

Vol 72 (2) ◽

pp. 636-641 ◽

Cited By ~ 35

Author(s):

R Anand ◽

CD Boehm ◽

HH Jr Kazazian ◽

EF Vanin

Keyword(s):

Transcriptional Start Site ◽

Globin Gene ◽

Event Analysis ◽

Beta Globin ◽

Base Pairs ◽

Dna Polymerase Alpha ◽

Beta Globin Gene ◽

American Black ◽

The Individual

Abstract We report the characterization of a beta zero-thalassemia in an American Black with unusually high HbA2 and HbF levels. Genomic southern analysis indicated that the individual was heterozygous for a deletion that began within the second intervening sequence of the beta- globin gene and extended approximately 1.4 kb in the 5′ direction. A clone spanning the breakpoint on the abnormal chromosome was isolated and further mapped, and the deletion joint was sequenced. Comparison of the normal beta-globin gene and its 5′ flanking region with the deletion joint sequence indicated that the 5′ breakpoint for this deletion was 484 base pairs (bp) 5′ to the transcriptional start site for the beta-globin gene and the 3′ breakpoint was 908 bp into the beta- globin gene; the deletion removed a total of 1,393 bp. Comparison of the normal 5′ and 3′ breakpoint sequences indicated that this deletion was the result of a “clean” nonhomologous breakage and reunion event; ie, no spurious bases were added during the recombinational event. Analysis of the breakpoints of this deletion together with the breakpoints of two other small deletions involving the beta-globin gene suggests that the breakpoints may occur at DNA polymerase alpha pause sites.

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SPECTRUM OF BETA GLOBIN GENE MUTATIONS IN EGYPTIAN CHILDREN WITH β- THALASSEMIA

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2014.071 ◽

2014 ◽

Vol 6 (1) ◽

pp. e2014071 ◽

Cited By ~ 6

Author(s):

MR El-Shanshory ◽

Adel Abd Elhaleim Hagag

Keyword(s):

Dna Sequencing ◽

Blood Count ◽

Complete Blood Count ◽

Globin Gene ◽

Gene Mutations ◽

Thalassemia Major ◽

Direct Dna Sequencing ◽

Rare Mutations ◽

Egyptian Children

Background: The molecular defects resulting in β-thalassemia phenotype, in the Egyptian population show a clear heterogenic mutations pattern. PCR based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis.The aim of the work: was to evaluate the different β-globin gene mutations in one hundred Egyptian children with β-thalassemia. Patients and Methods: One hundred of β-thalassemic Egyptian children, covering most Egyptian Governorates. All patients were subjected to meticulous history taking, clinical examinations, complete blood count, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of β-globin gene to detect the frequency of different mutations in studied patients. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)19%,IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C> T) 4%,-87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was considerable variation in phenotypic severity among patients resulting from interaction of different β° and β+mutations, 79(79%) patients were thalassemia major (TM) and 21(21%) were thassemia intermedia (TI), without genotype phenotype association. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in β- thalassemic patients including rare and /or unknown ones.

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The polyadenylation site mutation in the alpha-globin gene cluster

Blood ◽

10.1182/blood.v71.2.313.bloodjournal712313 ◽

1988 ◽

Vol 71 (2) ◽

pp. 313-319 ◽

Cited By ~ 1

Author(s):

SL Thein ◽

RB Wallace ◽

L Pressley ◽

JB Clegg ◽

DJ Weatherall ◽

...

Keyword(s):

Middle Eastern ◽

Globin Gene ◽

Saudi Arabian ◽

Polyadenylation Signal ◽

Enzyme Analysis ◽

Restriction Enzyme Analysis ◽

Site Mutation ◽

Mediterranean Populations ◽

Alpha Globin ◽

Hb H Disease

In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.

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Sequencing of the Canine Cytochrome P450 CYP2C41 Gene and Genotyping of Its Polymorphic Occurrence in 36 Dog Breeds

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.663175 ◽

2021 ◽

Vol 8 ◽

Author(s):

Emre Karakus ◽

Clarissa Prinzinger ◽

Silke Leiting ◽

Joachim Geyer

Keyword(s):

Cytochrome P450 ◽

Drug Metabolism ◽

Gene Deletion ◽

Homologous Sequence ◽

Pharmacokinetic Studies ◽

Metabolizing Enzymes ◽

Genomic Level ◽

Very High

Cytochrome P450 (CYP) drug metabolizing enzymes play an important role in efficient drug metabolism and elimination. Many CYPs are polymorphic and, thereby, drug metabolism can vary between individuals. In the case of canine CYP2C41, gene polymorphism was identified. However, as the first available canine genome sequences all were CYP2C41 negative, this polymorphism could not be clarified at the genomic level. The present study provides an exact characterization of the CYP2C41 gene deletion polymorphism at the genomic level and presents a PCR-based genotyping method that was used for CYP2C41 genotyping of 1,089 individual subjects from 36 different dog breeds. None of the Bearded Collie, Bernese Mountain, Boxer, Briard, French Bulldog or Irish Wolfhound subjects had the CYP2C41 gene in their genomes. In contrast, in the Chinese Char-Pei, Siberian Husky, Schapendoes and Kangal breeds, the CYP2C41 allele frequency was very high, with values of 67, 57, 43, and 34%, respectively. Interestingly, the site of gene deletion was identical for all CYP2C41 negative dogs, and all CYP2C41 positive dogs showed highly homologous sequence domains upstream and downstream from the CYP2C41 gene. CYP2C41 genotyping can now be routinely used in future pharmacokinetic studies in canines, in order to identify genetically-based poor or extensive drug metabolizers. This, together with more extensive in vitro drug screening for CYP2C41 substrates will help to determine the clinical relevance of CYP2C41, and to optimize drug treatment. Although the relative abundance of the CYP2C41 protein in the canine liver seems to not be very high, this CYP could substantially contribute to hepatic drug metabolism in dogs expressing CYP2C41 from both alleles and, when CYP2C41 shows higher catalytic activity to a given drug than other hepatic metabolic enzymes.

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